The Emory Alzheimer's Disease Research Center (ADRC) provides Georgia and the region with comprehensive clinical, research, and educational programs This renewal application outlines our success in building an environment that encourages and supports innovative projects directed at understanding the pathogenesis and developing new treatments for AD and other age-related cognitive disorders. We benefit from generous institutional support from Emory, one of the nation's fastest growing research academic enterprises, and collaborative interactions with the Emory Center for Neurodegenerative Disease, and the Yerkes National Primate Center. Our 5 cores demonstrate remarkable productivity in recruiting patients from the culturally diverse clinical specialty programs at Emory and Grady Memorial Hospitals for participation in our ADRC registry, the autopsy program, and the various clinical research activities. Data from these cores are captured and stored for distribution to local researchers and for national collaborations. Our biospecimen banks include well-characterized neuropathological case materials, and DNA, CSF, and blood samples from our clinical populations. These valuable resources are distributed widely for a variety of approved studies of genetic, molecular, pharmacological, and pathological investigations. The ADRC educational programs reach a broad audience of students, health care professionals, and the public. We propose three cutting edge research projects that are closely integrated with ADRC Cores: Project 1 (Dr. Ben Hampstead) "Comparison of Memory Rehabilitation Techniques in Mild Cognitive Impairment", will use a novel approach to rehabilitation of memory combining behavioral components with functional brain imaging to address whether rehabilitation techniques target the intended brain regions and to determine the signature of brain activity associated with successful rehabilitation. Project 2, "miRNA Expression Modulation of Alzheimer Disease Pathogenesis" (Dr. Peng Jin) will extend studies of miRNAs selectively altered in AD brain and evaluate their role in the post-transcriptional regulation of the expression of specific mRNAs that are involved in AD pathogenesis. Project 3, "Norepinephrine-TrkB Interactions in Alzheimer's Disease" (Dr. David Weinshenker) studies a novel interaction between catecholamines and the TrkB receptor in animal and cell culture models of AD, as well as in brain tissues obtained from controls, MCI, and AD cases. Collectively, these projects span clinical, translational, and basic science research and will advance our understanding of cognition in normal aging and its transitions to mild cognitive impairment, AD, and related neurodegenerative disorders.